Robot-Assisted Radical Nephroureterectomy Using the KangDuo-Surgical Robot-01 System: A Prospective, Single-Center, Single-Arm Clinical Study.

Purpose: To investigate the feasibility, safety, and efficacy of the KangDuo-Surgical Robot-01 (KD-SR-01) system for robot-assisted radical nephroureterectomy (RARNU). Materials and Methods: This prospective, single-center, single-arm clinical study of patients with upper tract urothelial carcinoma (UTUC) was conducted from August 2022 to July 2023 using the KD-SR-01 system. The perioperative and follow-up data were prospectively recorded. The National Aeronautics and Space Administration task load index was calculated to present ergonomics. The technique was described in detail. Results: A total of 13 patients underwent RARNU. None of the cases conversed to laparoscopic procedure or open procedure. The median docking time and console time were 524 seconds (range 139-963 seconds) and 102.2 minutes (range 55.3-249.3 minutes), respectively. The median estimated blood loss was 40 mL (range 10-100 mL). None of the patients required intraoperative blood transfusion. The median postoperative hospital stay was 4 days (range 2-7 days). Intraoperative or postoperative complications (Clavien-Dindo grade I) occurred in nine patients. The surgeon task load index global score achieved 1.05 ± 1.86. Three patients received the single-docking technique, demonstrating similar perioperative results compared with patients with redocking. The study is registered at www.chictr.org.cn (ChiCTR2200056672). Conclusions: The KD-SR-01 system was feasible, safe, and effective for RARNU.

Establishment and validation of a predictive model for the efficacy of repeated extracorporeal shock wave lithotripsy in patients with upper urinary calculi / 现代泌尿外科杂志

【Objective】 To analyze the independent influencing factors of repeated extracorporeal shock wave lithotripsy (ESWL) in the treatment of upper urinary calculi (UUC), based on which a nomogram model was established to predict the efficacy. 【Methods】 Clinical and imaging data of 203 patients receiving repeated ESWL during Jan.2020 and Dec.2022 were collected, including 117 cases in the successful group and 86 cases in the unsuccessful group.The patients’ age and sex, stone volume (SV), surface area (SA), skin-to-site distance (SSD), maximum CT value, mean stone density (MSD), and stone heterogeneity index (SHI) were compared between the two groups.The independent predictors were analyzed with logistic regression and the meaningful variables (P<0.05) were used to establish a nomogram.The efficacy of the model was evaluated using receiver operating characteristic (ROC) curve and decreasing curve analysis (DCA).Internal validation was also performed. 【Results】 Stepwise regression showed that SV, SSD, MSD and SHI were independent influencing factors (P<0.05).The area under the ROC curve (AUC), optimal threshold, sensitivity and specificity were 0.793 (95%CI: 0.674-0.911), 0.619, 77.1% and 74.0%, respectively.The DCA curve was above two extreme curves.Hosmer-Lemeshow test and calibration curve showed that the nomogram had a good fitting degree (χ2=5.526, P=0.489), and the correction C-index was 0.746. 【Conclusion】 SV, SSD, MSD and SHI are independent predictors of the efficacy of repeated ESWL in the treatment of UUC.The nomogram established based on the above indicators has good predictive efficiency and clinical applicability.

Effects of leonurine on the improvement of rats with severe acute pancreatitis by regulating HMGB1/RAGE signaling pathway / 中国药房

OBJECTIVE To study the effects of leonurine on pancreatic injury in rats with severe acute pancreatitis （SAP）， and to explore its mechanism based on the high-mobility group box 1 （HMGB1）/receptor for advanced glycation end products （RAGE） signaling pathway. METHODS SAP rat model was constructed by injecting 5% sodium taurocholate into the bile duct of the pancreas. Model rats were randomly divided into model group， low dose leonurine group （8 mg/kg）， high dose leonurine group （16 mg/kg）， HMGB1 overexpression group （8 μg/kg）， and high dose leonurine+HMGB1 overexpression group （16 mg/kg+8 μg/kg）， with 14 rats in each group. Another 14 rats were selected as the sham operation group. Rats in each group were injected with corresponding drugs or normal saline via abdominal cavity or tail vein once a day for 5 consecutive days. After the last administration， the levels of serum amylase （AMS） and lipase （LPS） were detected； the pathological injury of pancreatic tissue was observed； the levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， malondialdehyde （MDA） and superoxide dismutase （SOD）， mRNA and protein expressions of HMGB1 and RAGE in pancreatic tissues were detected. RESULTS Compared with model group， the structure of pancreatic tissue in rats gradually recovered in low and high dose leonurine groups； inflammatory cell infiltration gradually decreased； the pathological injury score and the levels of AMS， LPS， TNF-α， IL-6， MDA， the mRNA and protein expressions of HMGB1 and RAGE were significantly decreased， while the SOD levels were significantly increased （P＜0.05）. The high dose leonurine group showed more significant improvement （P＜0.05）； the pathological damage of pancreatic tissue in the HMGB1 overexpression group worsened， and except for a decrease in SOD levels， all other quantitative indicators increased significantly （P＜0.05）. Overexpression of HMGB1 could reduce the improvement effect of high dose leonurine on the above indexes in SAP rats （P＜0.05）. CONCLUSIONS Leonurine may alleviate pancreatic injury， inflammation and oxidative stress in pancreatic tissue of rats with SAP by inhibiting the HMGB1/RAGE signaling pathway.

Effects of norethindrone on the growth, behavior, and thyroid endocrine system of adult female western mosquitofish (Gambusia affinis).

Progestins are mainly used in pharmacotherapy and animal husbandry and have received increasing attention as they are widely detected in various aquatic ecosystems. In this study, adult female western mosquitofish (Gambusia affinis) were exposed to different concentrations of norethindrone (NET) (solvent control, 5.0 (L), 50.0 (M), and 500.0 (H) ng/L) for 42 days. Behaviors, morphological parameters, histology of the thyroid, thyroid hormone levels (TSH, T3, and T4), and transcriptional levels of nine genes in the hypothalamic-pituitary-thyroid (HPT) axis were examined. The results showed that NET decreased sociality but increased the anxiety of G. affinis. Sociality makes fish tend to cluster, and anxiety may cause G. affinis to reduce exploration of new environments. Female fish showed hyperplasia, hypertrophy, and glial depletion in their thyroid follicular epithelial cells after NET treatment. The plasma levels of TSH and T4 were significantly reduced, but T3 concentrations were significantly increased in the fish from the H group. In addition, the transcripts of genes (tshb, tshr, tg, dio1, dio2, thrb) in the brains of fish in the M and H treatments were significantly stimulated, while those of trh and pax2a were suppressed. Our results suggest that NET may impact key social behaviors in G. affinis and interfere with the entire thyroid endocrine system, probably via affecting the transcriptional expression of upstream regulators in the HPT axis.

Phytoextraction and Migration Patterns of Cadmium in Contaminated Soils by Pennisetum hybridum.

This study was conducted to identify soil cadmium (Cd) removal pathways and their contribution rates during phytoremediation by Pennisetum hybridum, as well as to comprehensively assess its phytoremediation potential. Multilayered soil column tests and farmland-simulating lysimeter tests were conducted to investigate the Cd phytoextraction and migration patterns in topsoil and subsoil simultaneously. The aboveground annual yield of P. hybridum grown in the lysimeter was 206 ton·ha-1. The total amount of Cd extracted in P. hybridum shoots was 234 g·ha-1, which was similar to that of other typical Cd-hyperaccumulating plants such as Sedum alfredii. After the test, the topsoil Cd removal rate was 21.50-35.81%, whereas the extraction efficiency in P. hybridum shoots was only 4.17-8.53%. These findings indicate that extraction by plant shoots is not the most important contributor to the decrease of Cd in the topsoil. The proportion of Cd retained by the root cell wall was approximately 50% of the total Cd in the root. Based on column test results, P. hybridum treatment led to a significant decrease in soil pH and considerably enhanced Cd migration to subsoil and groundwater. P. hybridum decreases Cd in the topsoil through multiple pathways and provides a relatively ideal material for phytoremediation of Cd-contaminated acid soils.

Iron oxide nanoparticles inhibit tumor growth by ferroptosis in diffuse large B-cell lymphoma.

Since the approval by the Food and Drug Administration (FDA), ferumoxytol and other iron oxide nanoparticles (IONs) have been widely used as iron supplements for patients with iron deficiency. Meanwhile, IONs have also been used as contrast agents in magnetic resonance imaging and as drug carriers. Importantly, IONs have demonstrated a significant inhibitory effect on the growth of tumors, including hematopoietic and lymphoid tumors, such as leukemia. In this study, we further demonstrated the effect of IONs on inhibiting the growth of diffuse large B-cell lymphoma (DLBCL) cells by enhancing ferroptosis-mediated cell death. IONs treatment caused an accumulation of intracellular ferrous iron and the onset of lipid peroxidation in DLBCL cells as well as the suppressed expression of anti-ferroptosis protein Glutathione Peroxidase 4 (GPX4), thereby leading to increased ferroptosis. Mechanistically, IONs increased cellular lipid peroxidation through the generation of ROS via the Fenton reaction and regulating the iron metabolism-related proteins, such as ferroportin (FPN) and transferrin receptor (TFR), which elevated the intracellular labile iron pool (LIP). Hence, our findings suggest the potential therapeutic effect of IONs on the treatment of patients with DLBCL.

[Effectiveness and Mechanisms of Chemical Leaching Combined with Electrokinetic Technology on the Remediation of Heavy Metal Contaminated Soil].

In this study, chemical leaching and electrokinetic technology were used to remediate heavy metal contaminated soil to elucidate its effectiveness and mechanisms. Chemical leaching agents of FeCl3, Fe(NO3)3, KCl, KNO3, and HCl solutions were selected, and the effects of Fe3+, K+, H+, and Cl- on four heavy metal (Cd, Pb, Cu, and Zn) removals were compared and analyzed. Then, the influence of the speciation of heavy metals in soil after chemical leaching on the electrokinetic remediation efficiency was studied. The results showed that Fe3+, K+, H+, and Cl- had different effects on the four heavy metal removals; for Cd and Zn, the removal effect of H+was the most effective, but for Pb and Cu, the effect of Fe3+ was the most obvious. On the whole, FeCl3 and Fe(NO3)3 showed the best removal effect for Cd, Pb, and Cu. For the removal of Zn from the soil, the difference in the removal effect of the five leaching agents was not obvious. In comparison with that of FeCl3 and Fe(NO3)3, the HCl solution had a moderate removal effect on the four heavy metals in the soil, and the neutral salts KCl and KNO3 had little removal effect on the four heavy metals. Especially for Cd and Cu, KCl and KNO3 addition significantly increased the removal of heavy metals through the subsequent electrokinetic remediation. After the chemical leaching, electrokinetic remediation could make heavy metals in the topsoil (0-10 cm) migrate downward and enrich the 10-20 cm and 20-30 cm soil layers, which requires further studies to resolve.

Field experiments to assess the remediation efficiency of metal-contaminated soil by flushing with ferric chloride followed by applying amendments.

The Cd, Cu, Pb, and Zn removal efficiencies achieved by flushing with FeCl3 were determined in a field experiment using soil contaminated with multiple metals. Soil was first flushed with FeCl3 and then with FeCl3 or a mixture of chelators. Flushed soil was amended with lime and organic matter to revitalize the soil, then the soil was used to grow Zea mays and Brassica juncea. The heavy metal concentrations in groundwater were determined to assess the risks of leaching caused by soil flushing. The Cd, Cu, Pb, and Zn removal efficiencies were 70%, 40%, 33%, and 17%, respectively, when FeCl3 (25 mmol (kg topsoil)-1) was applied. The second washing generally did not significantly decrease the heavy metal contents of the soil but the second FeCl3 washing did decrease the Pb content. Pb leached from topsoil was partly retained by the subsoil 20-40 cm deep. The Zea mays yields were significantly lower but the Brassica juncea yields were significantly higher after the combined soil flushing and amendment treatment than after only the amendment treatment. This indicated that soil flushing only negatively affected growth of deep-rooted Z. mays. The Cd, Cu, Pb, and Zn concentrations in Z. mays grains and the edible parts of B. juncea grown in remediated soil were below the Chinese tolerable limits for contaminants in food. Washing with FeCl3 did not increase groundwater contamination during the study. The results indicated that flushing soil with FeCl3 and subsequent amendments is a technically feasible method for remediating agricultural soil contaminated with Cd.

Shouwuwan Regulates Synaptic Plasticity of Hippocampal Neurons in Rat Model of D-galactose-induced Aging via mTOR Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Shouwuwan on the synaptic plasticity of hippocampal neurons in the rat model of D-galactose-induced aging via the mammalian target of rapamycin （mTOR） signaling pathway. MethodA total of 50 male SPF-grade SD rats were randomized into normal group， model group， vitamin E （0.018 g·kg-1） group， and low- and high-dose （1.08，2.16 g·kg-1， respectively） Shouwuwan groups. Except the normal group， the other four groups were treated with D-galactose （120 mg·kg-1） for the modeling of aging. The rats were simultaneously administrated with corresponding agents by gavage. After six weeks of modeling， Morris water maze test was carried out to examine the behavioral changes. The whole brain and hippocampus samples were collected. The expression of postsynaptic density protein-95 （PSD-95） and synaptophysin （SYN） in the hippocampus was detected by immunohistochemistry. Golgi staining was employed to observe the changes in the morphology and function of neurons. Western blot and Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） were respectively employed to determine the mRNA and protein levels of mTOR， phosphorylated （p）-mTOR， p70 ribosome protein S6 kinase （p70S6K）， phosphorylated （p）-p70S6K， eukaryotic translation initiation factor 4E-binding protein 2 （4EBP2）， and phosphorylated （p）-4EBP2 in the hippocampus. ResultCompared with the normal group， the model group showed slow swimming （P<0.01）， extended total swimming distance （P<0.05）， prolonged latency （P<0.01）， and decreased crossing number （P<0.01）. The modeling inhibited the expression of PSD-95 and SYN in the CA1 region of the hippocampus （P<0.01）， with the weakest staining effect and the smallest region， decreased the intersections of hippocampal neuron dendrites with concentric circles at the concentric distance of 100， 140， 180， and 200 μm from the cell body （P<0.01）， and reduced the length and density of dendritic spine （P<0.01）. In addition， the modeling up-regulated the mRNA levels of mTOR and p70S6K and the protein levels of p-mTOR and p-p70S6K （P<0.01） and down-regulated the mRNA level of 4EBP2 and the protein levels of 4EBP2 and p-4EBP2 （P<0.01）. Compared with the model group， low- and high-dose Shouwuwan increased the average swimming speed （P<0.01）， shortened the latency （P<0.01）， increased the crossing number （P<0.01）， promoted the expression of PSD-95 and SYN in the hippocampal CA1 region （P<0.01）， increased the intersections between hippocampal neuronal dendrites and concentric circles at the concentric distance of 100， 140， 180，200 μm from the cell body （P<0.01）， and increased the number， length， and density of dendritic spine （P<0.01）. Furthermore， Shouwuwan down-regulated the protein levels of p-mTOR and p-p70S6K （P<0.01）， up-regulated the protein levels of 4EBP2 and p-4EBP2 （P<0.05，P<0.01）， down-regulated the mRNA levels of mTOR and p70S6K （P<0.01）， and up-regulated the mRNA level of 4EBP2 （P<0.01）. ConclusionShouwuwan can improve the learning and memory ability of rats exposed to D-galactose， promote the expression of proteins associated with synaptic plasticity， improve the morphology of neurons， repair neural function， reduce neuronal apoptosis， and inhibit mTOR signaling pathway to delay brain aging.

Screening of housekeeping genes in Gelsemium elegans and expression patterns of genes involved in its alkaloid biosynthesis / 生物工程学报

Gelsemium elegans is a traditional Chinese herb of medicinal importance, with indole terpene alkaloids as its main active components. To study the expression of the most suitable housekeeping reference genes in G. elegans, the root bark, stem segments, leaves and inflorescences of four different parts of G. elegans were used as materials in this study. The expression stability of 10 candidate housekeeping reference genes (18S, GAPDH, Actin, TUA, TUB, SAND, EF-1α, UBC, UBQ, and cdc25) was assessed through real-time fluorescence quantitative PCR, GeNorm, NormFinder, BestKeeper, ΔCT, and RefFinder. The results showed that EF-1α was stably expressed in all four parts of G. elegans and was the most suitable housekeeping gene. Based on the coexpression pattern of genome, full-length transcriptome and metabolome, the key candidate targets of 18 related genes (AS, AnPRT, PRAI, IGPS, TSA, TSB, TDC, GES, G8H, 8-HGO, IS, 7-DLS, 7-DLGT, 7-DLH, LAMT, SLS, STR, and SGD) involved in the Gelsemium alkaloid biosynthesis were obtained. The expression of 18 related enzyme genes were analyzed by qRT-PCR using the housekeeping gene EF-1α as a reference. The results showed that these genes' expression and gelsenicine content trends were correlated and were likely to be involved in the biosynthesis of the Gelsemium alkaloid, gelsenicine.

Effectiveness of arthroscopic autologous iliac bone grafting with double-row elastic fixation for recurrent anterior shoulder dislocation with massive glenoid bone defect / 中国修复重建外科杂志

OBJECTIVE@#To investigate the effectiveness of arthroscopic autologous iliac bone grafting with double-row elastic fixation in treatment of recurrent anterior shoulder dislocation combined with massive glenoid bone defects.@*METHODS@#Between January 2018 and December 2021, 16 male patients with recurrent anterior shoulder dislocation combined with massive glenoid bone defects were treated with arthroscopic autogenous iliac bone grafting and double-row elastic fixation. The patients were 14-29 years old at the time of the first dislocation, with an average age of 18.4 years. The causes of the first dislocation included falling injury in 5 cases and sports injury in 11 cases. The shoulders dislocated 4-15 times, with an average of 8.3 times. The patients were 17-37 years old at the time of admission, with an average age of 25.1 years. There were 5 left shoulders and 11 right shoulders. The preoperative instability severity index (ISIS) score of the shoulder joint was 5.8±2.1, and the Beighton score was 4.3±2.6. The University of California Los Angeles (UCLA) score, Constant score, American Shoulder and Elbow Surgeons (ASES) score, and Rowe score were used to evaluate shoulder function, and the degree of the glenoid bone defect repair was observed based on CT after operation.@*RESULTS@#All incisions healed by first intention, and no complication such as incision infection or neurovascular injury occurred. The patients were followed up 12 months. At 12 months after operation, UCLA score, Constant score, ASES score, and Rowe score all significantly improved when compared with the scores before operation ( P<0.05). CT imaging showed the degree of glenoid bone defect was significantly smaller at immediate, 6 and 12 months after operation when compared with that before operation ( P<0.05), and the bone blocks healed with the scapula, and bone fusion had occurred at 12 months.@*CONCLUSION@#Arthroscopic autologous iliac bone grafting with double-row elastic fixation is a safe treatment for recurrent anterior shoulder dislocation combined with massive glenoid bone defects, with good short-term effectiveness.

Radical therapy with or without chemotherapy in highly malignant non-metastatic prostate cancer: interim analysis of a prospective non-randomized controlled study / 中华放射肿瘤学杂志

Objective:To compare the efficacy and safety of standard treatment with or without adjuvant chemotherapy in patients with highly malignant non-metastatic prostate cancer.Methods:In this prospective non-randomized controlled study, consecutive non-metastatic prostate cancer patients with pathologically proven Gleason score of 9-10 or Gleason score of 5 admitted to Peking University First Hospital were enrolled. Four to six cycles of chemotherapy using docetaxel ± carboplatin regimen were added or not after standard radical therapy. The primary end point was 5-year event-free survival (EFS), and the secondary end points were distant metastasis-free survival (MFS), overall survival (OS), and treatment-related adverse events. The survival curve was drawn by Kaplan-Meier method. The differences between two groups were analyzed by log-rank test.Results:A total of 176 patients were consecutively enrolled from November 2019 to January 2022 of which 138 patients received only standard radical therapy (control group), and 38 patients received adjuvant chemotherapy after standard radical therapy (chemotherapy group). The median follow-up time was 13.4 (2.0-34.0) months. All patients survived. The 30-month EFS rates in the chemotherapy and control groups were 100% and 85.6%, respectively ( P=0.064). There were no events in the chemotherapy group, while there were 12 cases of events in the control group, including 6 cases of biochemical recurrence and 6 cases of imaging progression. The 30-month MFS rates in two groups were 100% and 91.9%, respectively ( P=0.205). After the 1 vs. 2 propensity score matching, the EFS and MFS rates in two groups were 100% vs. 85.7% ( P=0.056), and 100% vs. 92.2% ( P=0.209), respectively. The incidence rates of grade 2 and above urinary toxicity in the chemotherapy and control groups were 2.6% and 7.2% ( P=0.354), respectively. The incidence rates of grade 2 and above rectal toxicity were 5.3% and 5.1% ( P=0.711), respectively. Grade 3 and above chemotherapy-related toxicity in the chemotherapy group were leukopenia (31.6%), thrombocytopenia (2.6%) and alopecia (13.2%). Conclusion:The addition of adjuvant chemotherapy after standard radical therapy tends to improve the overall EFS of patients with highly malignant prostate cancer, and the adverse effects are tolerable, which should be confirmed by long-term follow-up results.

Application of a novel urine DNA predictor for non-invasive early diagnosis and monitoring minimal residual disease in upper tract urothelial carcinoma / 中华泌尿外科杂志

Objective:To study the value of urine-based multi-dimensional bioinformatics evaluation model (utLIFE model) in early diagnosis and postoperative monitoring of upper urinary tract urothelial carcinoma (UTUC).Methods:Morning urine samples of patients clinically diagnosed with UTUC without bladder cancer from Peking University First Hospital from August 2022 to October 2022 were collected. Urine samples were collected before and after surgery, and DNA was extracted for gene sequencing. The utLIFE model previously constructed by our center was used to calculate the score, based on 155 gene mutation sites and copy number variation, and the score ≥60 was defined as utLIFE positive. The sensitivity of utLIFE model in diagnosis of UTUC was analyzed with postoperative pathology as the gold standard. The utLIFE scores before and after operation were also compared.Results:A total of 53 patients were included in this study, all of whom were confirmed as UTUC by postoperative pathology. The median age of patients was 66 (59, 72) years. Twenty-four cases (45.3%) of UTUC tumors were located in the renal pelvis, 26 cases (49.1%) were located in the ureter, and 2 cases (5.7%)involved both ureter and renal pelvis. There were 27 patients (50.9%) at T 1stage and 26 patients (49.1%) at ≥T 2 stage. Preoperative utLIFE score of 53 patients was 79 (70, 84). The sensitivity of preoperative utLIFE diagnosis of UTUC was 96.2% (51/53). utLIFE showed similar high sensitivity in T 1 stage and ≥T 2 stage [100.0% (27/27) vs. 92.3% (24/26), P=0.236], in N 0 and ≥N 1 stage [ 95.0% (38/40) vs. 100.0% (5/5), P=1.000]. In addition, the sensitivity of preoperative utLIFE was higher than that of urine cytology [ 95.2% (20/21) vs. 23.8% (5/21). P<0.001], fluorescence in situ hybridization (FISH) [ 92.6% (25/27) vs. 55.5% (15/27), P=0.004] and ureteroscopy [ 86.7% (13/15) vs. 60.0% (9/15), P=1.000]. A total of 45 patients postoperative utLIFE samples were collected, and the postoperative utLIFE score was significantly lower than that of preoperative [ 36 (18, 61) vs. 79 (70, 84), P<0.001]. Conclusions:utLIFE, as a non-invasive urine DNA bioinformatics assessment model, is significantly superior to cytology and FISH in early detection and has high sensitivity in diagnosis of UTUC, and can reflect perioperative minimal residual disease levels.

Simultaneous determination of six constituents in Xiao'er Qingyan Granules by HPLC / 中成药

AIM To establish an HPLC method for the simultaneous content determination of monocaffeyltartaric acid,forsythiaside A,chicoric acid,phillyrin,arctiin and harpagoside in Waigan Fenghan Granules.METHODS The analysis of 70%methanol extract of this drug was performed on a 30℃thermostatic Agilent Zorbax SB-C18 column(250 mm×4.6 mm,5 μm),with the mobile phase comprising of acetonitrile-0.1%phosphoric acid flowing at 1.0 mL/min in a gradient elution manner,and the detection wavelengths were set at 278,330 nm.RESULTS Six constituents showed good linear relationships within their own ranges(r≥0.999 4),whose average recoveries were 96.80%-102.61%with the RSDs of 0.26%-1.93%.CONCLUSION This simple and accurate method can be used for the quality control of Xiao'er Qingyan Granules.

Mechanism of Danggui Sini Decoction in improving kidney injury caused by blood stasis syndrome based on metabolomics and network pharmacology / 中国中药杂志

This article analyzed the mechanism of Danggui Sini Decoction(DSD) in improving kidney injury caused by blood stasis syndrome(BSS) in rats. Firstly, 32 female SD rats were randomly divided into the following four groups: a normal group and a BSS group, both receiving an equal amount of distilled water by gavage; a normal+DSD group and a BSS+DSD group, both receiving 5.103 g·kg~(-1) DSD orally for a total of 14 days. Daily cold water bath was given to establish the BSS model, and on the 14th day, BSS rats were subcutaneously injected with 0.8 mg·kg~(-1) adrenaline. Normal rats were subjected to the water bath at 37 ℃ and injected with an equal volume of distilled water. After the experiment, 24-hour urine, serum, and kidney samples were collected for metabolomic analysis, biochemical measurements, and hematoxylin-eosin(HE) staining. The study then employed ~1H-NMR metabolomic technology to reveal the metabolic network regulated by DSD in improving BSS-induced kidney injury and used network pharmacology to preliminarily elucidate the key targets of the effectiveness of DSD. Pathological and biochemical analysis showed that DSD intervention significantly reduced inflammation and abnormal levels of blood creatinine, blood urea nitrogen, and urine protein in the kidneys. Metabolomic analysis indicated that DSD attenuated BSS-induced kidney injury primarily by regulating 10 differential metabolites and three major metabolic pathways(taurine and hypotaurine metabolism, citrate cycle, and acetaldehyde and dicarboxylic acid metabolism). Network pharmacology analysis suggested that the protective effect of DSD against BSS-induced kidney injury might be related to two key genes, ATP citrate lyase(ACLY) and nitric oxide synthase 2(NOS2), and two main metabolic pathways, i.e., arginine biosynthesis, and arginine and proline metabolism. This study, from the perspective of network regulation, provides initial insights and evidence into the mechanism of DSD in improving kidney injury induced by BSS, offering a basis for further investigation into the molecular mechanisms underlying its efficacy.

Role and mechanisms of CHI3L1 in coronary artery lesions in a mouse model of Kawasaki disease-like vasculitis / 中国当代儿科杂志

OBJECTIVES@#To explore the role and potential mechanisms of chitinase-3-like protein 1 (CHI3L1) in coronary artery lesions in a mouse model of Kawasaki disease (KD)-like vasculitis.@*METHODS@#Four-week-old male SPF-grade C57BL/6 mice were randomly divided into a control group and a model group, with 10 mice in each group. The model group mice were intraperitoneally injected with 0.5 mL of lactobacillus casei cell wall extract (LCWE) to establish a mouse model of KD-like vasculitis, while the control group mice were injected with an equal volume of normal saline. The general conditions of the mice were observed on the 3rd, 7th, and 14th day after injection. Changes in coronary artery tissue pathology were observed using hematoxylin-eosin staining. The level of CHI3L1 in mouse serum was measured by enzyme-linked immunosorbent assay. Immunofluorescence staining was used to detect the expression and localization of CHI3L1, von Willebrand factor (vWF), and α-smooth muscle actin (α-SMA) in coronary artery tissue. Western blot analysis was used to detect the expression of CHI3L1, vWF, vascular endothelial cadherin (VE cadherin), Caspase-3, B cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax), nuclear factor κB (NF-κB), and phosphorylated NF-κB (p-NF-κB) in coronary artery tissue.@*RESULTS@#The serum level of CHI3L1 in the model group was significantly higher than that in the control group (P<0.05). Compared to the control group, the expression of CHI3L1 in the coronary artery tissue was higher, while the expression of vWF was lower in the model group. The relative expression levels of CHI3L1, Bax, Caspase-3, NF-κB, and p-NF-κB were significantly higher in the model group than in the control group (P<0.05). The relative expression levels of vWF, VE cadherin, and Bcl-2 were lower in the model group than in the control group (P<0.05).@*CONCLUSIONS@#In the LCWE-induced mouse model of KD-like vasculitis, the expression levels of CHI3L1 in serum and coronary arteries increase, and it may play a role in coronary artery lesions through endothelial cell apoptosis mediated by inflammatory reactions.

Procedures for application of the extended dosing after antitumor drug clinical trials / 中南大学学报(医学版)

New drug clinical trials have been considered as a positive way for treating cancer by cancer patients and doctors, and the extended dosing is a special way for patients' withdrawal from antitumor clinical trials to obtain investigational new drugs. However, neither the regulations of expanded dosing nor the detail documents for expanded dosing have been officially published in China. At present, expanded dosing of investigational drugs is still at the exploratory stage in various medical institutions, and a complete management system has not been established to meet patients' urgent needs for drug use. Based on the practical experience of extended dosing in Hunan Cancer Hospital, this paper preliminarily explored the application procedures and ethical review requirements of extended dosing for subjects in antitumor clinical trials. It is necessary to clarify the responsibilities of all patients in the procedure and establish a patient-medical institution-sponsor joint application system. In the process of ethical review, it is recommended that all parties fully consider the risks and benefits of extended dosing for patients, and then the ethics committee makes a comprehensive assessment to decide whether to approve extended dosing.

[Research Progress of Abnormal Iron Metabolism and Tumor of Lymphatic Hematopoiesis System --Review].

Iron metabolism is the process of absorption, transport, storage and conversion and excretion of the essential trace element iron in living organisms. Normal iron metabolism tightly regulates iron content at the systemic and cellular levels through a variety of related proteins to prevent excessive free radicals from being generated during the iron cycle that can damage the body. Various abnormalities in iron metabolism are found in a variety of lymphohaematopoietic tumours and an insidious link between iron metabolism and tumour development has been revealed. Serum ferritin levels and abnormalities of iron transport proteins, transferrin and their receptors can be used as prognostic indicators for lymphohematopoietic tumours and have opened up new directions of diagnosis and treatment, with a large number of novel drugs targeting tumours emerging to date. This article briefly describes the normal iron metabolism process and highlights the progress of research on abnormal iron metabolism in lymphohematopoietic tumors at the systemic and cellular levels.

CC chemokine receptor 2 (CCR2) expression promotes diffuse large B-Cell lymphoma survival and invasion.

In recent years, CC chemokine receptor 2 (CCR2) has been found to be involved in tumor growth, angiogenesis, epithelial mesenchymal transition, metastasis, and immune escape. CCR2 overexpression was first identified as a poor prognostic predictor in diffuse large B-cell lymphoma (DLBCL) in our published article, but the mechanisms involved remain unknown. In this work, we collected data from another 138 patients with DLBCL data and verified the CCR2 expression level and its relationship to clinicopathological characteristics. Furthermore, we explored the possible mechanisms via in vitro and in vivo experiments. We showed that CCR2 overexpression was an independent prognostic marker and predicted shorter overall survival (OS) and progression-free survival (PFS) in patients with DLBCL. Blockade of CCR2 expression with a CCR2 antagonist inhibited tumor cell proliferation, migration, and anti-apoptosis ability in vitro by affecting the PI3K/Akt signaling pathway and the p38 MAPK signaling pathway. Furthermore, administration of a CCR2 antagonist decreased tumor growth and dissemination of DLBCL cells and increased survival time in the xenograft model. Our study demonstrates that CCR2 expression plays an important role in the development of DLBCL by stimulating cell proliferation, migration, and anti-apoptosis. Therefore, the inhibition of CCR2 may be a potential target for anticancer therapy in DLBCL.

Evaluation of manganese application after soil stabilization to effectively reduce cadmium in rice.

In order to produce safe rice from cadmium (Cd) contaminated soils, a special pot experiment in the field was proposed to facilitate the study of multiple remediation measures. In the field experiments, four treatments were selected for the first half of the year: rice without soil treatment (R); rice with zeolite stabilization (RZ); oilseed rape phytoremediation (OR); and inter-cropping Sedum alfredii and maize phytoremediation (IC). As the early rice with zeolite stabilization still contained elevated Cd, manganese (Mn) fertilizer was added in the late rice with a special pot experiment in the field. Results showed that, in the first crops, the grains of maize and oilseed rape contained Cd below the food standard limit, while Cd in rice grain exceeded the limit of 0.2 mg/kg. The RZ treatment did not reduce Cd in rice but decreased significantly Mn in rice straw. In the late rice, Mn fertilizer additionally reduced Cd in rice grain to 0.12 mg/kg in combination with the RZ treatment. Mn accumulation in rice straw was enhanced by Mn fertilizer. These results indicate that the pot experiment in the field provides a useful tool to further evaluate effective treatment combinations to reduce Cd in rice.